16-50321998-G-T

Position:

• chr16-50321998-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_013263.5(BRD7):​c.1484C>A​(p.Thr495Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BRD7 NM_013263.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.855

Genes affected

BRD7 (HGNC:14310): (bromodomain containing 7) This gene encodes a protein which is a member of the bromodomain-containing protein family. The product of this gene has been identified as a component of one form of the SWI/SNF chromatin remodeling complex, and as a protein which interacts with p53 and is required for p53-dependent oncogene-induced senescence which prevents tumor growth. Pseudogenes have been described on chromosomes 2, 3, 6, 13 and 14. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054781348).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRD7	NM_013263.5	c.1484C>A	p.Thr495Lys	missense_variant	13/17	ENST00000394688.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRD7	ENST00000394688.8	c.1484C>A	p.Thr495Lys	missense_variant	13/17	1	NM_013263.5	P4
BRD7	ENST00000394689.2	c.1484C>A	p.Thr495Lys	missense_variant	13/17	1		A1
BRD7	ENST00000710357.1	c.1607C>A	p.Thr536Lys	missense_variant	13/17
BRD7	ENST00000710356.1	c.1535C>A	p.Thr512Lys	missense_variant	13/17

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 10, 2024

The c.1484C>A (p.T495K) alteration is located in exon 13 (coding exon 13) of the BRD7 gene. This alteration results from a C to A substitution at nucleotide position 1484, causing the threonine (T) at amino acid position 495 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Benign	0.76
DEOGEN2	Benign	0.033	T;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.65	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.055	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;L
MutationTaster	Benign	0.99	N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.070	N;N
REVEL	Benign	0.024
Sift	Benign	0.90	T;T
Sift4G	Benign	0.90	T;T
Polyphen		0.21	B;B
Vest4		0.16
MutPred		0.31		Gain of ubiquitination at T495 (P = 0.0029);Gain of ubiquitination at T495 (P = 0.0029);
MVP		0.45
MPC		0.19
ClinPred		0.12	T
GERP RS		1.1
Varity_R		0.025
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs753971768; hg19: chr16-50355909;